codeine phosphate/guaifenesin er tablet 30 mg/600 mg steady state clinical study

Conditions: Cough

Summary: the objectives of this pivotal study are: 1. to evaluate bioavailability of an extended-release and immediate release codeine phosphate/guaifenesin tablet at steady state following multiple oral administration 2. to assess the safety and tolerability of this codeine phosphate/guaifenesin extended release formulation.

this study will be a single-center, two-site open-label, randomized, multiple-dose, two-treatment, two-period crossover design. during the course of the study, thirty eight (38) healthy adult volunteers will receive multiple doses of codeine phosphate/ guaifenesin extended-release tablet 30 mg/600 mg and multiple doses of an ir codeine phosphate/ guaifenesin immediate-release tablet 20 mg/400 mg tablet in two separate treatment periods. volunteers will enter the clinic the day prior \[approximately 12 hours\] to each dosing and will be confined in the clinic for 7 nights for each treatment period. the extended release tablet (test) will be administered as two tablets two times a day, 12 hours apart, and the immediate release tablet (reference) will be administered as one tablet six times a day, 4 hours apart. pre-dose blood samples will be collected prior to morning dose on days 1, 2, 3, 4, 5, 6 and 7. on day 7, two extended release tablets will be given once in the morning and the immediate release tablet will be given three times, in the morning and 4 and 8 hours later. serial blood samples will be collected on day 7 for up to 12 hours post morning dose. on day 7 volunteers will be released from the study site after the 12-hour blood collection if clinically appropriate and will return to the study site to start the next treatment after a minimum of 7 days of wash-out period, which begins the morning after the last dose taken of the previous period.

Eligibility criteria:
inclusion criteria: * healthy non-smoking volunteers (female volunteers on a stable contraceptive medication regimen (\> 3 months) may continue during the course of the study but its use must be documented), 18 to 45 years of age, inclusive; ethnic group: arab \& mediterranean. * race: mixed skin (white \& black skin people). * body mass index (bmi) between 18 and 32 kg/m2, inclusive (minimum of 50 kg weight); * willing and able to comply with the appropriate instructions necessary to complete the study, and; * fully informed of the risks of entering the study and willing to provide written informed consent. * subject is available for the whole study period and gave written informed consent * if female, must be practicing abstinence or using a medically acceptable form of contraception (e.g., intrauterine device, hormonal birth control \[continuously used for at least 3 months before first dose\], or double barrier method). for the purpose of this study, all females are considered to be of childbearing potential unless they have been post - menopausal, biologically sterile, or surgically sterile (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation) for more than one (1) year * normal physical examination. * vital signs within normal ranges. * all laboratory screening results within the normal range, or being assessed as clinically non-significant by the attending physician. * normal kidney and liver functions test. exclusion criteria: * • women of childbearing potential who don't use any contraceptive method, pregnant and/or lactating women. * ethnic group (non- arab \&/ or non- mediterranean) * a significant abnormality in the pre-study physical examination that would place the volunteer at risk during participation in the trial; * a clinical laboratory test value outside of the accepted reference range that is deemed by the investigator to be clinically significant; * require prescription medication on a regular basis; * a clinically significant illness during the 28 days prior to period 1 dosing (as determined by the investigator); * history of serious illness that can impact fate of drugs * history of gastrointestinal obstruction, constipation, inflammatory bowel disease, gallbladder disease, pancreas disorder over last 2 years, or recent (over last 3 years) gastrointestinal tract surgery, including gall bladder resection; * known history or presence of cardiac, pulmonary, endocrine, musculoskeletal, neurological, hematological or disease. * subjects with acute pulmonary insufficiency, respiratory depression, acute or chronic severe respiratory insufficiency or history of any of these * history of head injury, seizures over last 4 years deemed by the investigator to be clinically significant; * mental disease * history of kidney disease or urination problem over last 2 years deemed by the investigator to be clinically significant * subjects with renal and/or hepatic insufficiency should be excluded * presence of any significant physical or organ abnormality * history of low blood pressure is deemed by the investigator to be clinically significant; * a positive hepatitis b surface antigen, hepatitis c antibody screen, or a reactive hiv antibody screen; * known or suspected hypersensitivities, allergies, or other contraindications to codeine or a related opioid and/or guaifenesin; * history of severe allergy or allergic reactions to study drug or related drugs or heparin * known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs * known or suspected history of drug abuse within lifetime as judged by the investigator; * history of alcohol abuse or excessive intake of alcohol within last 5 years as judged by the investigator; * positive screen for drugs of abuse, alcohol, or cotinine (nicotine) at screening or on admission to the unit prior to administration of investigational products; * use of drugs that induce or inhibit the hepatic metabolizing cytochrome p450 2d6 enzymes, within 30 days prior to administration of study formulations. examples of inducers include: piperidins, carbamazepine, dexamethasone, rifampin. examples of inhibitors include: cimetidine, diphenhydramine, fluvastatine, methadone, and ranitidine; * use of prescription medications within 21 days and otc medications (including vitamins or herbal products) within 7 days (excluding flu vaccination) prior to the first administration of the study medication without sponsor approval; * intake of alcohol 48 before each study drug administration, and caffeine, or xanthine beverages 24 hrs before each study drug administration. * use of any investigational drug within 30 days prior to first dosing; * use of any tobacco-containing product within 6 months of first dosing; * donated more than 400 ml of blood within 4 weeks before first dosing; * participation in another bioequivalence study and/or clinical trials within 80 days prior to the start of this study period i * exhausting physical exercise in the last 48 hours (e.g. weight lifting) or any recent significant change in dietary or exercise habits. * abnormal vital signs * abnormal kidney and liver functions test. * in the opinion of the investigator, unlikely or unable to successfully complete the study; * volunteer is vegetarian. * vomiting, diarrhea on admission.